An examination procedure known as ultrasonography or sonography is used clinically to delineate bodily structures by ultrasonic imaging. But progress and practical applications of diagnostic ultrasonic imaging have been delayed by the lack of effective clinically usable imaging agents. This is especially the case with respect to ultrasonic imaging agents for the gastrointestinal tract.
Ultrasonic imaging utilizes an ultrasonic scanner to generate and receive sound waves. The scanner is placed on a body surface overlying the area to be imaged, and sound waves are directed toward that area. The scanner detects reflected sound wave and translates that data into images. When ultrasonic energy propagates through an inhomogeneous substance, the acoustic properties of the substance determine the degree of absorption, scattering, and transmission of the ultrasound. As ultrasound waves propagate through one medium to another, there is some degree of reflection at the interface. The degree of reflection is related to the acoustic properties of each material, which properties are determined primarily by the material's density and the speed of sound transmission through the material.
Contrast agents for diagnostic ultrasound were reviewed by Ophir and Parker, Ultrasound in Med. & Biol. (1989), 15:319-333. Various contrast agents are described for intravascular administration and imaging. These include free and encapsulated gas bubbles, colloidal suspensions, emulsions, and aqueous solutions. Different mechanisms which can enhance image contrast are discussed; namely, backscatter contrast, attenuation contrast, and speed of sound contrast. Orally administrable ultrasound contrast agents are not discussed. With respect to the development of parenteral imaging agents, the authors observed that the development "has been slow and sporadic, and to date there are no completely satisfactory materials for clinical imaging." In the concluding paragraph, the authors added: "The clinical need for ultrasound contrast agents is high, but much interdisciplinary research, covering acoustic material properties, imaging, biochemistry, histology, toxicology and related specialties will be required before ultrasound contrast agents are commercially available and in routine clinical use."
Particulate suspensions have been used as vascular contrast agents in radiography. For this purpose, radiopaque particles are employed. A particulate contrastmaterial is described by Parker et al., Ultrasound in Med. & Biol. (1987), 13:555-566. The agent proposed for intravenous injection consisted of an iodipamide ethyl ester in the form of dense, relatively incompressible solid collagen particles. A theoretical description of backscatter versus particle size is found in Morse and Ingard, "Theoretical Acoustics", 1986, (Princeton University Press, Princeton, N.J.). It was proposed that such particles might enhance the ultrasound image by relative motion attenuation and/or backscatter attenuation.